Heroin abuse can promote the high incidence of infectious disease and HIV seropositivity in drug users by functioning as cofactors to alter host immune function, incidence of infection, and eventual development of AIDS in this population. Heroin is a powerful reinforcer, stimulating reward-seeking behavior associated with profound changes in central nervous system neurotransmitters and neuroanatomical sites which may subserve immune function. We propose to extend our previous studies on experimenter-delivered opioid effects on immune function. We plan to provide an analysis of the behavioral and neurochemical consequences of response- dependent (self-administered) versus response-independent (yoked) drug presentation on immune function. These studies have relevance to certain aspects of the involvement of self-administered heroin in health and disease in addicts. We will correlate response- dependent with response-independent effects of heroin on the immune system through analysis of surface antigens, cytokine production, and functional studies of leukocytes. In addition, we plan to investigate central neurotransmitter systems and peripheral endocrine pathways associated with immune function alterations in animals self-administering hero in and appropriate controls. Our research plan is designed to add important information regarding the regulation and control of immune function through central opiatergic mechanisms in drug abusers. This will enhance our understanding of the effects of heroin abuse on aspects of the central nervous system, endocrine function, and define the role of opiatergic systems in physiological regulation and suppression of immune function in pathological and disease states. These studies may provide avenues for novel treatments where opiatergic systems are implicated in HIV infection and the high incidence of AIDS in intravenous heroin users.